Neural stimulation system and method responsive to collateral neural activity

ABSTRACT

A neural stimulation system responsive to collateral neural activity that may arise in association with a neural stimulation procedure includes a stimulation interface configured to deliver stimulation signals to a target neural population, a monitoring interface positioned to receive signals corresponding to a neural activity within the target neural population, a stimulus unit coupled to deliver stimulation singals to the stimulation interface, and a sensing unit coupled to the monitoring device and the stimulus unit. The neural stimulation procedure may be directed toward rehabilitating, restoring, and/or enhancing one or more neural functions by facilitating and/or effectuating a neuroplastic change or reorganization; and/or affecting a neurological condition that exists on a continuous or essentially continuous basis absent the stimulation procedure. The sensing unit determines whether evidence of an collateral neural activity exists, whereupon the stimulus unit attempts to abate the collateral neural activity.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a continuation of Ser. No. 12/941,577, filed Nov. 8,2010, pending, which is a divisional of U.S. application Ser. No.10/271,394, filed Oct. 15, 2002, now U.S. Pat. No. 7,831,305, which is acontinuation-in-part of U.S. application Ser. No. 09/978,134, filed Oct.15, 2001, now U.S. Pat. No. 7,305,268, which is a continuation-in-partof U.S. application Ser. No. 09/802,808, filed Mar. 8, 2001, whichclaims the benefit of U.S. Provisional Application No. 60/217,981, filedJul. 13, 2000, the disclosures of which are incorporated herein byreference.

TECHNICAL FIELD

The present disclosure is related to systems and methods for detectingand responding to collateral neural activity that may arise inassociation with or as a result of stimulation applied to a region ofthe cortex or other area of the brain.

BACKGROUND

A wide variety of mental and physical processes are controlled orinfluenced by neural activity in particular regions of the brain. Forexample, the neural-functions in some areas of the brain (i.e., thesensory or motor cortices) are organized according to physical orcognitive functions. There are also several other areas of the brainthat appear to have distinct functions in most individuals. In themajority of people, for example, the areas of the occipital lobes relateto vision, the regions of the left interior frontal lobes relate tolanguage, and the regions of the cerebral cortex appear to beconsistently involved with conscious awareness, memory, and intellect.

Many problems or abnormalities with body functions can be caused bydamage, disease and/or disorders in the brain. Effectively treating suchabnormalities may be very difficult. For example, a stroke is a verycommon condition that damages the brain. Strokes are generally caused byemboli (e.g., obstruction of a vessel), hemorrhages (e.g., rupture of avessel), or thrombi (e.g., clotting) in the vascular system of aspecific region of the brain, which in turn generally cause a loss orimpairment of a neural function (e.g., neural functions related tofacial muscles, limbs, speech, etc.). Stroke patients are typicallytreated using various forms of physical therapy to rehabilitate the lossof function of a limb or another affected body part. Stroke patients mayalso be treated using physical therapy plus drug treatment. For mostpatients, however, such treatments are not sufficient, and little can bedone to improve the function of an affected body part beyond the limitedrecovery that generally occurs naturally without intervention.

The neural activity in the brain can be influenced by electrical energythat is supplied from a waveform generator or other type of device.Various patient perceptions and/or neural functions can thus be promotedor disrupted by applying an electrical current to the cortex or otherregion of the brain. As a result, researchers have attempted to treatvarious neurological conditions using electrical or magnetic stimulationsignals to control or affect brain functions.

Neural activity is governed by electrical impulses or “actionpotentials” generated in and propagated by neurons. While in a quiescentstate, a neuron is negatively polarized, and exhibits a resting membranepotential that is typically between −70 and −60 mV. Through electricalor chemical connections known as synapses, any given neuron receivesfrom other neurons excitatory and inhibitory input signals or stimuli. Aneuron integrates the excitatory and inhibitory input signals itreceives, and generates or fires a series of action potentials in theevent that the integration exceeds a threshold potential. A neuralfiring threshold may be, for example, approximately −55 mV. Actionpotentials propagate to the neuron's synapses, where they are conveyedto other neurons to which the neuron is synaptically connected.

A neural stimulation signal may comprise a series or train of electricalor magnetic pulses that deliver an energy dose to neurons within atarget neural population. The stimulation signal may be defined ordescribed in accordance with stimulation signal parameters includingpulse amplitude, pulse frequency, duty cycle, stimulation signalduration, and/or other parameters. Electrical or magnetic stimulationsignals applied to a population of neurons can depolarize neurons withinthe population toward their threshold potentials. Depending uponstimulation signal parameters, this depolarization can cause neurons togenerate or fire action potentials. Neural stimulation that elicits orinduces action potentials in a functionally significant proportion ofthe neural population to which the stimulation is applied is referred toas supra-threshold stimulation; neural stimulation that fails to elicitaction potentials in a functionally significant proportion of the neuralpopulation is defined as sub-threshold stimulation. In general,supra-threshold stimulation of a neural population triggers or activatesone or more functions associated with the neural population, butsub-threshold stimulation by itself fails to trigger or activate suchfunctions. Supra-threshold neural stimulation can induce various typesof measurable or monitorable responses in a patient. For example,supra-threshold stimulation applied to a patient's motor cortex caninduce muscle fiber contractions.

While electrical or magnetic stimulation of neural tissue may bedirected toward producing an intended type of neural activity, suchstimulation may result in unintended collateral neural activity. Inparticular, neural stimulation for treating a condition can induceseizure activity or other types of collateral neural activity. It willbe appreciated that such collateral neural activity is undesirableand/or inconvenient in a neural stimulation situation.

Seizure activity may originate at a seizure focus, which is typically acollection of neurons (e.g., on the order of 1000 neurons) exhibiting acharacteristic type of synchronous firing activity. In particular, eachneuron within a seizure focus exhibits a firing response known as aparoxysmal depolarizing shift (PDS). The PDS is a large magnitude, longduration depolarization that triggers a neuron to fire a train or burstof action potentials. Properly functioning feedback and/or feed-forwardinhibitory signaling mechanisms cause afterhyperpolarization throughwhich the neuron's membrane potential returns to a hyperpolarized statebelow its firing threshold. Following afterhyperpolarization, the neuronmay undergo another PDS.

Afterhyperpolarization limits the duration of the PDS, thereby helpingto ensure that synchronous neural firing activity remains localized tothe seizure focus. Inhibitory feedback signaling provided by neuronssurrounding a seizure focus, commonly referred to as “surroundinhibition,” is particularly important in constraining seizure activityto the seizure focus. In the event that inhibitory signaling mechanismsfail and/or are unable to overcome or counter PDS activity, neuronswithin the seizure focus recruit other neurons to which they aresynaptically coupled into their synchronous firing pattern. As a result,synchronous firing activity spreads beyond the seizure focus to otherareas of the brain. This can lead to a cascade effect in which seizureactivity becomes increasingly widespread, and accompanying clinicalmanifestations become increasingly significant.

In view of the foregoing, it may be important to detect and/or respondto seizure activity. Various systems and/or devices directed towardtreating neurological conditions exist, including those capable ofdetecting and responding to particular types of neurological events. Forexample, some neural stimulators attempt to treat involuntary motiondisorders such as Parkinson's disease by applying stimulation signals tothe thalamus or other area of a patient's brain. As another example,U.S. Pat. No. 6,134,474 describes an implantable device capable ofdetecting a neurological event, such as seizure activity, and generatinga responsive electrical signal intended to terminate the detected event.Additionally, European Patent Application Publication EP1145736describes an implantable device capable of detecting electrical activityin the brain; applying a nonresponsive signal to reduce the likelihoodof a seizure occurring; and applying a responsive signal in the eventthat epileptiform activity is detected.

Unfortunately, present neural stimulation systems and methods fail toautomatically detect and/or respond to seizure activity or othercollateral neural activity induced in association with and/or as aresult of neural stimulation procedures directed toward purposes otherthan epileptic seizure management. In particular, conventional neuralstimulation systems fail to automatically detect seizure activityinduced by neural stimulation procedures directed toward patient neuralfunction rehabilitation and/or enhancement, or modulation of patientsensory perceptions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a neural stimulation systemresponsive to specific neural activity according to an embodiment of theinvention.

FIG. 2 is a graph illustrating several parameters that may describe orcharacterize a stimulation signal.

FIG. 3A is a plan view of a grid electrode configured as a stimulationinterface according to an embodiment of the invention.

FIG. 3B is a plan view of an implantable stimulation and monitoringinterface configured for stimulating a target neural population anddetecting signals corresponding to specific neural activity according toan embodiment of the invention.

FIG. 4 is a flowchart of a neural stimulation process responsive tospecific neural activity according to an embodiment of the invention.

FIG. 5 is a flowchart of a neural stimulation process responsive tospecific neural activity according to another embodiment of theinvention.

FIG. 6 is a flowchart of a neural stimulation process responsive tospecific neural activity according to another embodiment of theinvention.

DETAILED DESCRIPTION

The following disclosure describes a system and method for detecting andresponding to collateral neural activity that may arise in associationwith and/or as a result of a neural stimulation procedure. In thecontext of the present invention, a neural stimulation procedure mayinvolve the application of stimuli to one or more target neuralpopulations within a patient, and may be directed toward rehabilitating,restoring, and/or enhancing one or more neural functions in the patientby facilitating and/or effectuating a neuroplastic change orreorganization. A neural stimulation procedure may alternatively oradditionally be directed toward modulating or ameliorating a patientsensory perception such as pain, or affecting a neurological conditionthat is present on a continuous or essentially continuous basis in theabsence of the applied stimuli. Collateral neural activity may compriseseizure activity, migraine activity, and/or essentially any other typeof neural activity that may be undesirable, unwanted, unintended, and/orcounterproductive relative to an intended or desired neural activity oroutcome associated with the neural stimulation procedure.

FIG. 1 is a schematic illustration of a neural stimulation system 100for detecting and responding to collateral neural activity according toan embodiment of the invention. In one embodiment, the system 100comprises a stimulus unit 140 configured to deliver stimulation signalsto a patient 190 using a stimulation interface 110. The system 100 mayadditionally comprise a sensing unit 180 configured to identify ordetect parameters associated with collateral neural activity in thepatient 190 using a monitoring interface 112. The sensing unit 180 isconfigured to communicate with the stimulus unit 140 upon detection ofcollateral neural activity and/or periodically throughout a stimulationprocedure. The stimulus unit 140 may be coupled to the stimulationinterface 110 by a first link 114; the monitoring interface 112 may becoupled to the sensing unit 180 by a second link 116; and the sensingunit 180 may be coupled to the stimulus unit 140 by a third link 118,where one or more of such links 114, 116, 118 may be wire-based orwireless.

The stimulus unit 140 generates and outputs stimulation signals. Asconsidered herein, stimulation signals may include treatment signalsand/or response signals. Treatment signals may comprise electricaland/or magnetic stimuli applied to one or more target neural populationsand directed toward treating and/or rehabilitating one or moreneurological conditions. The treatment signals may also affect orinfluence particular types of neurological activity. In general,treatment signals may be directed toward affecting or altering one ormore neurological conditions that exist within the patient 190 on acontinuous, essentially continuous, or nearly continuous basis (i.e.,non-intermittent or essentially non-intermittent through potentiallycyclical) in the absence of the treatment signal. Treatment signals maybe directed toward facilitating and/or effectuating neuroplasticity inthe patient 190, for example, in a manner described in U.S. patentapplication Ser. No. 09/978,134, which is incorporated herein byreference. Treatment signals may alternatively or additionally bedirected toward affecting or modulating a patient sensation such aspain; or eliminating or ameliorating the effects of neurodegenerativedisorders, for example, involuntary movements and/or other symptomsassociated with Parkinson's disease.

In general, response signals may comprise electrical, magnetic, and/orother (e.g., sonic or vibratory) stimuli directed toward disrupting,desynchronizing, abating, and/or eliminating collateral neural activityarising in association with or as a result of the application oftreatment signals to the patient 190. Depending upon their nature,response signals may be applied proximate or directly to one or moretarget neural populations and/or particular patient sensory systems orbody locations. The description that follows considers electromagneticresponse signals; however, the present invention may employ other oradditional types of response signals in a manner understood by thoseskilled in the art.

FIG. 2 is a graph illustrating several parameters that may define,describe, or characterize stimulation signals. A stimulus start time t₀defines an initial point at which a stimulation signal is applied to thestimulation interface 110. In one embodiment, the stimulation signal maybe a biphasic waveform comprising a series of biphasic pulses, and whichmay be defined, characterized, or described by parameters including apulse width t₁ for a first pulse phase; a pulse width t₂ for a secondpulse phase; and a pulse width t₃ for a single biphasic pulse. Theparameters can also include a stimulus repetition rate 1/t₄corresponding to a pulse repetition frequency; a stimulus pulse dutycycle equal to t₃ divided by t₄; a stimulus burst time t₅ that defines anumber of pulses in a pulse train; and/or a pulse train repetition rate1/t₆ that defines a stimulus burst frequency. Other parameters include apeak current intensity I₁ for the first pulse phase and a peak currentintensity I₂ for the second pulse phase. Those skilled in the art willunderstand that pulse intensity or amplitude may decay during one orboth pulse phases, and a pulse may be a charge-balanced waveform. Thoseskilled in the art will further understand that in an alternateembodiment, pulses can be monophasic or polyphasic. Additionalstimulation parameters may include applying the stimulation to selectedconfigurations of the stimulation interface 110 for any givenstimulation signal and/or time.

In one embodiment, the stimulus unit 140 comprises a controller 150, apulse system 160, and a set of controls/indicators 170. The controller150 may include a processor, a memory, and a programmable computermedium. The controller 150 may be implemented as a computer ormicrocontroller, and the programmable medium can be hardware and/ormemory resident software that performs, directs, and/or facilitatesneural stimulation procedures in accordance with the present invention.The controls/indicators 170 can include a graphic user interface, aninput/output device, and/or other types of interface elements forexchanging commands and/or output with the controller 150.

The pulse system 160 selectively generates stimulation signals andsends, directs, or delivers such stimuli to the stimulation interface110. The pulse system 160 may be implanted into the patient 190, in amanner described in U.S. application Ser. No. 09/802,808 incorporatedherein by reference. Alternatively, the pulse system 160 may be anexternal unit capable of delivering stimulation signals to thestimulation interface 110 using RF energy, electromagnetism, or wireterminals exposed on the patient's scalp. The stimulation interface 110may comprise one or more stimulus delivery devices configured to applytreatment signals and/or response signals to the patient 190. Thestimulation interface 110 may comprise a type of neural-stimulationdevice described in U.S. application Ser. No. 09/802,808.

In one embodiment, the pulse system 160 is a component of a TranscranialMagnetic Stimulation (TMS) device that delivers magnetic stimulationsignals to a patient 190. The stimulation interface 110 in thisembodiment may comprise an electromagnetic coil arrangement in a mannerunderstood by those skilled in the art. In another embodiment, the pulsesystem 160 forms a portion of an electrical stimulation device. Thestimulation interface 110 of this embodiment may comprise an electrodearrangement or configuration capable of delivering electricalstimulation signals to the patient 190. In such an embodiment, thestimulation interface 110 may be implanted into the patient 190 toprovide cortical stimulation, deep brain stimulation, and/or other typesof neural stimulation.

Various portions or elements of the stimulation interface 110 may beconfigured to deliver treatment signals only, response signals only, oreither treatment or response signals. One or more portions of thestimulation interface 110 may reside upon or proximate to one or moretarget neural populations in and/or through which a) neuroplasticity maybe occurring and/or may be expected to occur; and/or b) a patientsensation such as pain may be modulated or influenced.

FIG. 3A is a plan view of an exemplary grid electrode 120 capable ofimplementing one or more portions of a stimulation interface 110according to an embodiment of the invention. The grid electrode 120comprises a support member or substrate 122 that carries a plurality ofelectrical contacts 124. Those skilled in the art will understand thatthe number of contacts 124 may vary in accordance with embodimentdetails. The grid electrode 120 further comprises a set of leads (notshown) that couple the contacts 124 to the pulse system 160 in a mannerunderstood by those skilled in the art. A grid electrode 120 of the typeshown in FIG. 3A is available from AdTech Medical Instrument Corporationof Racine, Wis. (www.adtechmedical.com).

The contacts 124 can be divided so that one group of contacts 124delivers treatment signals while another group of contacts 124 deliversresponse signals. For example, a central contact group 126 may delivertreatment signals to a target neural population while an outer contactgroup 128 may deliver response signals in a manner that may enhance orpromote surround inhibition. In such an embodiment, response signals maybe delivered in a time-shared or a concurrent manner relative totreatment signal delivery. Alternatively, the grid electrode 120 may beconfigured to deliver treatment signals or response signals to allcontacts 124 in a time-shared manner, or configured to deliver treatmentsignals only or response signals only.

The sensing unit 180 comprises a system, device, or apparatus configuredto detect or identify collateral neural activity or parameters of suchactivity that occur in association with and/or as a result of a neuralstimulation procedure. The sensing unit 180 may include a processor, amemory, and a programmable computer medium. The programmable medium ofthe sensing unit 180 can comprise hardware and/or software capable ofanalyzing signals corresponding to neural activity and determiningwhether collateral neural activity or evidence of such activity exists.The sensing unit 180 may communicate with the stimulus unit 140 upondetecting collateral neural activity so that the stimulus unit 140 mayrespond to the sensing unit 180. The sensing unit 180 may monitor forcollateral neural activity or evidence of such activity on a periodic orcontinuous basis. The sensing unit 180, for example, can operate underthe direction of or in cooperation with the controller 150.Communication between the stimulus unit 140 and the sensing unit 180 mayoccur through the third link 118. Such communication may involve theexchange of operational parameters, synchronization information, statusinformation, and/or information associated with the detection ofcollateral neural activity.

The sensing unit 180 may receive from the monitoring interface 112 oneor more types of physiological signals and/or physiological correlatesignals useful for indicating the presence of collateral neuralactivity. In general, a meaningful, significant and/or sustained changein a physiological or physiological correlate signal relative to thesignal's normal or background behavior can indicate the onset and/oroccurrence of collateral neural activity. The sensing unit 180 maycomprise hardware and/or software that performs signal filtering,processing, and/or analysis operations. Depending upon the nature of thephysiological and/or physiological correlate signals underconsideration, the sensing unit 180 and/or the monitoring interface 112may exhibit various embodiments.

The monitoring interface 112 can have several embodiments. For example,one or more portions of the monitoring interface 112 may be oriented orpositioned relative or proximate to a set of target neural populationsto which a neural stimulation procedure is directed so that themonitoring interface 112 may detect or receive signals corresponding orrelated to such neural populations. Alternatively or additionally, oneor more portions of the monitoring interface 112 may be oriented orpositioned within or upon the patient's body to detect one or more typesof patient responses correlated to neural activity.

In one embodiment, the sensing unit 180 comprises anelectroencephalogram (EEG) monitoring and/or analysis device and themonitoring interface 112 comprises one or more surface, cortical, and/orsubcortical electrodes, electrode arrays, and/or electrical probescapable of receiving or detecting EEG signals. The sensing unit 180 mayanalyze EEG signals received from the monitoring interface 112 anddetermine whether collateral neural activity or evidence of suchactivity exists. Those skilled in the art will recognize that particulartypes of EEG activity, such as interictal spikes and/or energy spectrumshifts, may be indicative of seizure activity.

In addition to EEG signals, other types of physiological signals and/orphysiological correlate signals may be useful for providing evidence ofcollateral neural activity. For example, signals corresponding tocerebral blood flow (CBF) may be used to indicate the onset oroccurrence of seizure activity, as described by M. E. Weinand et al. inan article entitled “Cerebral blood flow and temporal lobeepileptogenicity” (J. Neurosurg. 1997 February; 86(2): 226-32). In oneembodiment, the monitoring unit 112 may comprise a CBF monitor, whichmay include a set of electrodes, a thermistor, and/or a thermaldiffusion probe; a set of near infrared sources and sensors; a set ofpiezoelectric ultrasonic emitters and sensors (to facilitate, forexample, transit time measurements); and/or one or more other types ofCBF monitoring devices. In such an embodiment, the sensing unit 180 maycomprise a CBF signal analysis system or device. In a related alternateembodiment, the monitoring unit 112 may comprise a neural tissueoxygenation monitor, and the sensing unit 180 may correspondinglycomprise a neural tissue oxygenation analysis system or device.

Particular types of muscle fiber activity may also be indicative ofcollateral neural activity (e.g., extremely rapid muscle fibercontractions, particularly when sustained). In one embodiment, thesensing unit 180 comprises an electromyography (EMG) device configuredto detect, monitor, and/or analyze motor evoked potentials (MEPs)associated with muscle fiber innervation, in a manner understood bythose skilled in the art. The monitoring interface 112 correspondinglycomprises a set of surface, percutaneous, and/or implanted electrodes orprobes that may be positioned or configured to measure electricalactivity associated with the innervation of one or more muscles and/ormuscle groups. In another embodiment, the sensing unit 180 comprises amotion analysis system and the monitoring interface 112 comprises a setof motion detectors, strain gauges, and/or accelerometers configured todetect or monitor one or more types of patient movements. The sensingunit 180 may analyze motion signals received from the monitoringinterface 112 and determine whether patient motions under considerationare indicative of seizure activity.

In other embodiments, the sensing unit 180 and monitoring interface 112may comprise one or more types of neural imaging systems, such as afunctional Magnetic Resonance Imaging (fMRI) system, a Positron EmissionTomography (PET) system, and/or a Magnetoencephalography (MEG) system.In general, the sensing unit 180 and/or the monitoring interface 112 maybe configured to receive, detect, monitor, measure, and/or analyze oneor more types of signals useful of indicating the presence of collateralneural activity.

The stimulation interface 110 and the monitoring interface 112 may beimplemented as devices and/or modules that reside upon physicallyseparate substrates or carriers positioned within and/or upon thepatient 190. Alternatively or additionally, one or more portions of suchinterfaces 110, 112 may be implemented together upon a singleimplantable carrier or substrate.

FIG. 3B is a plan view of an implantable stimulation and monitoringinterface 130 configured for stimulating a target neural population anddetecting signals corresponding to neural activity according to anembodiment of the invention. In one embodiment, the stimulation andmonitoring interface 130 comprises a support member 132 carrying astimulating element 134 and a monitoring element 136. The stimulatingelement 134 may comprise one or more electrodes organized in accordancewith a particular pattern, and the monitoring element 126 may comprise aset of electrodes and/or a CBF monitoring device positioned proximate oradjacent to the stimulating element 134. A set of leads 138 may couplethe stimulating element 134 and the monitoring element 136 to thestimulus unit 140 and the sensing unit 180, respectively. A stimulationand monitoring interface 120 may be positioned or oriented within apatient 190 such that a stimulating element 124 can deliver or applystimulation signals to one or more particular target neural populations,and the monitoring element 126 can detect signals indicative of neuralactivity associated with the targeted neural populations.

As previously indicated, one or more portions of the monitoringinterface 112 may comprise an electrode arrangement, which may include agrid electrode 120 of the type shown in FIG. 3A, a deep brain electrode,and/or one or more other electrode types. As a result, a stimulation andmonitoring interface 130 may comprise a grid electrode 120 of the typeshown in FIG. 3A. In such an embodiment, particular contacts 124 withinthe grid electrode 120 may be designated for neural activity monitoringand other contacts 124 may be configured to deliver treatment and/orresponse signals.

Depending upon the nature of the monitoring interface 112, the deliveryof stimulation signals to a target neural population may interfere withthe detection of signals corresponding to neural activity. As a result,the controller 150 and/or the pulse system 160 may periodicallyinterrupt a neural stimulation procedure, such that during stimulationprocedure interruptions, the sensing unit 180 may analyze signalsreceived from the monitoring interface 112 relative to collateral neuralactivity. Outside of such interruptions, the sensing unit 180 may beprevented from receiving or processing signals received from themonitoring interface 112. Alternatively, the sensing unit 180 maycompensate for the presence of stimulation signals, for example, throughsignal subtraction and/or other compensation operations, to facilitatedetection of collateral neural activity or evidence of collateral neuralactivity simultaneous with the delivery of stimulation signals to atarget neural population.

In embodiments in which a neural stimulation procedure is periodicallyinterrupted to facilitate detection of collateral neural activity orevidence of such activity, the stimulation and monitoring interface 120may be implemented using a single electrode arrangement or configurationin which any given electrode element used to deliver stimulation signalsduring the neural stimulation procedure may also be used to detectneural activity during a neural stimulation procedure interruption.Thus, the stimulation interface 110 and the monitoring interface 112 mayphysically be one and the same.

One or more portions of the controller 150, the pulse system 160, thestimulation interface 110, monitoring interface 112, and/or the sensingunit 180 can be integrated into a single implantable stimulationdelivery, monitoring, and/or management apparatus in a manner identicalanalogous or similar to the devices described in U.S. application Ser.No. 09/802,808. Such an integrated apparatus may be configured forimplantation into a patient's skull so that the stimulation interface110 and/or the monitoring interface 112 can contact the patient's duramatter or pia matter in one or more cortical regions. An integratedapparatus of this type can have an internal power source that can beimplanted into the patient 190, and/or an external power source coupledto the pulse system 160 via electromagnetic coupling or a directconnection.

FIG. 4 is a flowchart of a neural stimulation process 400 responsive tocollateral neural activity according to an embodiment of the invention.In one embodiment, the process 400 begins with a stimulation operation402 by initiating or continuing a neural stimulation procedure in whichstimulation signals are delivered to one or more target neuralpopulations within a patient 190 in accordance with a given set ofstimulation signal parameters. After initiating the stimulationoperation 402, the process 400 also includes a detection query 404 thatdetermines whether collateral neural activity or evidence of suchactivity exists. The detection query 404 may be performed in asimultaneous or sequential manner relative to the stimulation operation402. If collateral neural activity or evidence thereof does not exist,the process 400 continues with a termination query 406 that decideswhether the neural stimulation procedure is complete. If the process isnot complete, the process 400 returns to the stimulation operation 402;otherwise, if the process 400 is complete, it is terminated. If thedetection query 404 the process 400 determines that collateral neuralactivity exists, the process 400 halts the neural stimulation procedurein a termination operation 410, and generates and/or issues anotification signal indicative of such activity in a notificationprocedure 412. Following the notification procedure 412, the process 400ends.

FIG. 5 is a flowchart of a neural stimulation process 500 responsive tocollateral neural activity according to another embodiment of theinvention. In one embodiment, the process 500 begins with a stimulationoperation 502 by initiating or continuing a neural stimulation procedurein which stimulation signals are delivered to one or more target neuralpopulations within a patient 190 in accordance with a first set ofstimulation signal parameters. Next, the process 500 includes adetection query 504 that determines whether collateral neural activityor evidence thereof exists. If not, the process 500 proceeds to atermination query 506 to determine whether the neural stimulationprocedure is complete. If the neural stimulation procedure is notcomplete, the process 500 returns to the stimulation procedure 502;otherwise, the stimulation process 500 is terminated.

If collateral neural activity or evidence of such activity exists, theprocess 500 includes a termination operation 510 that halts the neuralstimulation procedure and a notification procedure 512 that generatesand/or issues a notification signal indicative of such activity. Thestimulation process 500 proceeds to a collateral activity query 520 thatsubsequently determines whether the collateral neural activity has beenabated or eliminated. If so, the process 500 proceeds to a query 530that determines whether to resume the neural stimulation procedure. Sucha determination may be based upon, for example, an elapsed time betweeninitiation of a neural stimulation procedure and detection of collateralneural activity; stored information characterizing and/or specifyingfrequency and/or history information associated with detection ofcollateral neural activity in the patient 190 undergoing the neuralstimulation procedure; an authorization signal received from a doctor ortherapist through the controls/indicators 170; and/or other information.

If resumption of the neural stimulation procedure is to occur, theprocess 500 continues with a modification operation 532 in which one ormore stimulation signal parameters may be modified. Such a modificationmay involve changing (e.g., decreasing) a stimulation current level orintensity; changing (e.g., increasing) a stimulation signal pulserepetition frequency; and/or modifying one or more other parametersshown in FIG. 2. Following the modification operation 532, the process500 includes time query 534 to determine whether a minimum time intervalhas elapsed. The time query 534 may provide a quiescent period duringwhich the patient's neural activity becomes predominantly normal and/orrepresentative of an acceptable baseline condition. If a minimum timeinterval has not elapsed, the process 500 remains at the time query 534;otherwise, the process 500 returns to the stimulation operation 502.

If the collateral activity query 520 determines that collateral neuralactivity has not been abated, the process 500 proceeds with a responsequery 540 that determines whether to apply to the patient 190 one ormore response signals directed toward abating or terminating thecollateral neural activity. If not, the process 500 ends. Otherwise, theprocess 500 proceeds with a signal selection procedure 542 thatdetermines one or more appropriate response signal types andcorresponding signal parameters, and a response procedure 544 thatapplies one or more response signals to the patient 190. Responsesignals may include one or more neural stimulation and/or other types ofsignals applied to the patient 190 through the stimulation interface110. Following the response procedure 544, the process 500 returns tothe stimulation operation 520.

As previously indicated, a neural stimulation procedure in accordancewith the present invention may facilitate and/or effectuate neuroplasticchange or reorganization within a patient 190, which in turn mayrehabilitate, restore, and/or enhance one or more patient neuralfunctions and/or behaviors. To facilitate and/or effectuateneuroplasticity, a neural stimulation procedure may be performedcooperatively with a behavioral therapy, such as described in U.S.application Ser. No. 90/802,808. A behavioral therapy may encompass, forexample, physical therapy, cognitive therapy, and/or a variety ofbehavioral tasks.

FIG. 6 is a flowchart of a neural stimulation process 600 responsive tocollateral neural activity according to another embodiment of theinvention. Relative to FIG. 5, like reference numbers indicate likesteps. In one embodiment, the process 600 begins with a stimulationoperation 602 by initiating or continuing a neural stimulation procedurein conjunction or association with a behavioral therapy. During thestimulation operation 602, stimulation signals are delivered to one ormore target neural populations within a patient 190 in accordance with afirst set of stimulation signal parameters. Following the stimulationoperation 602, other steps within the process 600 may proceed in mannersdescribed above with reference to FIG. 5.

From the foregoing, it will be appreciated that specific embodiments ofthe invention have been described herein for purposes of illustration,but that various modifications may be made without deviating from thespirit and scope of the invention. Accordingly, the invention is notlimited except as by the appended claims.

1. A neural stimulation system for neurostimulation of a patient,comprising: a first set of electrodes configured to be positioned upon atarget neural population corresponding to a site at whichneuroplasticity is occurring, a site at which neuroplasticity isexpected to occur, and/or a site associated with neuropathic pain; amonitoring device to receive signals corresponding to a neural activitywithin a portion of the target neural population, wherein the neuralactivity is related to an undesired collateral effect of stimulation ofthe target neural population; a stimulus unit coupled to deliver stimulito the first set of electrodes, the stimuli comprising a plurality ofgroups of pulses occurring according to a burst frequency, wherein (i)multiple pulses are generated within each respective group according toa pulse repetition frequency, (ii) adjacent groups within the pluralityof groups are spaced apart from each other in time with a substantiallyquiescent period; and a sensing unit coupled receive signals from themonitoring device. wherein the sensing unit is further coupled to thestimulus unit and the stimulus unit is adapted to vary a burstcharacteristic of the stimuli in response to feedback from the sensingunit.
 2. The neural stimulation system of claim 1 wherein the stimulusunit modifies a burst frequency of the stimuli in response to thefeedback from the sensing unit.
 3. The neural stimulation system ofclaim 1 wherein the stimulus unit modifies the pulse repetitionfrequency in response to the feedback from the sensing unit.
 4. Theneural stimulation system wherein the stimulus unit and the sensing unitare adapted for implantation within the patient.
 5. The neuralstimulation system of claim 1 wherein the monitoring device comprises asecond set of electrodes.
 6. The neural stimulation system of claim 1,wherein the monitoring device comprises a cerebral blood flow monitor.7. A method of reducing seizure activity during neural stimulation totreat a neural condition in a patient comprising: applying electricalstimuli to a target neural population within the patient by positioningat least a first set of electrodes in contact with the patient's duramatter or pia matter, the electrical stimuli directed to altering theneural condition other than a seizure, the electrical stimuli comprisinga plurality of groups of pulses occurring according to a burstfrequency, wherein (i) multiple pulses are generated within eachrespective group according to a pulse repetition frequency, (ii)adjacent groups within the plurality of groups are spaced apart fromeach other in time with a substantially quiescent period; monitoring aparameter associated with seizure activity; determining if seizureactivity is present; reducing seizure activity, if present, byperforming modifying at least one burst characteristic of the electricalstimuli.
 8. The method of claim 7 wherein the monitoring a parameterassociated with seizure activity comprises monitoring anelectrophysiological signal of the patient.
 9. The method of claim 7wherein the monitoring a parameter comprises monitoring cerebral bloodflow.
 10. The method of claim 7 wherein the neural condition comprisespain.
 11. The method of claim 7 wherein the neural condition comprises afunctional deficit.
 12. The method of claim 7 wherein the reducingmodifies the burst frequency of the stimuli in response to the feedbackfrom the sensing unit.
 13. The method of claim 7 wherein the reducingmodifies the pulse repetition frequency in response to the feedback fromthe sensing unit.